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Biomarkers of preterm deliveries in the first trimester: exosomal placenta-specific microRNA

Research Project

Project/Area Number 19K18650
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionJichi Medical University

Principal Investigator

Takahashi Hironori  自治医科大学, 医学部, 教授 (80544303)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords絨毛膜栄養膜 / 妊娠高血圧腎症 / 妊娠糖尿病 / バイオマーカー / エクソソーム / サイトカインアレイ / インフラマソーム / 肥満 / 妊娠高血圧症候群 / 早産 / 絨毛外栄養膜 / サイトカイン / グロースファクター / マイクロRNA / 分娩 / microRNA / 産科学
Outline of Research at the Start

妊娠28週未満の超早産は新生児死亡や脳性麻痺の主原因であり、超早産の減少は周産期学の最重要課題である。しかし、その機構は不明であり、これを検出するバイオマーカーも存在しない。
そこで本研究では、エクソソーム中胎盤特異的miRNAの機能と早産マーカーとしての意義を明らかにするために、1)超早産例と非超早産例における胎盤特異的miRNAの発現量を比較する、2)妊娠初期に血液採取し、後に早産の有無で胎盤特異的miRNA発現量を比較する、3)胎盤絨毛栄養膜を用い、胎盤特異的miRNAを増減させ、EVT浸潤能や蛋白質変化を解析する。本研究は早産の病態解明とハイリスク患者の同定に役立つと期待される。

Outline of Final Research Achievements

1. Exosomes were extracted from pregnant women's plasma using ultracentrifugation. CD63 had been the most common exosome marker of pregnant women; however, it did’t express in pregnant women's plasma. Alternatively, CD9 constantly expressed and can be a novel plasma-derived exosome marker. We also showed that exosomes in women with preeclampsia significantly increased.
2. Cytokine arrays were performed using plasmas in patients with gestational diabetes mellitus and their controls. Of those, we focused on CXCL5. we examined plasma CXCL5 levels using ELISA (380 cases). No significant differences between the two groups were noted.
3. β-hydroxybutyrate (BHB) inhibits the activation of the NLRP3 inflammasome in women wih preeclampsia using trophoblast cells. It can reduce the progression of preterm delivery or preeclampsia.

Academic Significance and Societal Importance of the Research Achievements

妊娠初期血漿を集積し、その後に発症した妊娠合併症とコントロールを用い、バイオマーカーの探索を行った。血漿中の蛋白だけでなく、エクソソームにも研究範囲を広げ、探索した。今回明らかにした知見の中では妊婦血漿のエクソソームマーカーとして、CD9を用いることが、最も有用であることを示したことは特筆すべき事項である。従来は血漿(血清)中のエクソマーカーとしてはCD9以外を用いているものが多く、これらを再検証する必要性が示唆された。超早産例等のバイオマーカーは見付けるところまで至らず、今後の研究課題である。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results) Funded Workshop (2 results)

  • [Journal Article] Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1b secretion and hypertension via the NLRP3 inflammasome.2022

    • Author(s)
      Ozeki A, Oogaki Y, Henmi Y, Karasawa T, Takahashi M, Takahashi H, Ohkuchi A, Shirasuna K
    • Journal Title

      J Hypertens

      Volume: 40 Issue: 1 Pages: 84-93

    • DOI

      10.1097/hjh.0000000000002981

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] β-hydroxybutyrate suppresses NLRP3 inflammasome-mediated placental inflammation and lipopolysaccharide-induced fetal absorption.2021

    • Author(s)
      Hirata Y, Shimazaki S, Suzuki S, Henmi Y, Komiyama H, Kuwayama T, Iwata H, Karasawa T, Takahashi M, Takahashi H, Shirasuna K
    • Journal Title

      J Reproductive Immunology

      Volume: 148 Pages: 103433-103433

    • DOI

      10.1016/j.jri.2021.103433

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] LncRNA H19-derived miR-675-5p accelerates the invasion of extravillous trophoblast cells by inhibiting GATA2 and subsequently activating matrix metalloproteinases2021

    • Author(s)
      Ogoyama M, Ohkuchi A, Takahashi H, Zhao D, Matsubara S, Takizawa T
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 3 Pages: 1237-1237

    • DOI

      10.3390/ijms22031237

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extravillous trophoblast invasion accelerated by WNT3A, 5A, and 10B via CD442019

    • Author(s)
      Takahashi H, Ogoyama M, Nagayama S, Suzuki H, Ohkuchi A, Matsubara S, Takizawa T
    • Journal Title

      The Journal of Maternal-Fetal & Neonatal Medicine

      Volume: 印刷中 Issue: 20 Pages: 1-9

    • DOI

      10.1080/14767058.2019.1684891

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 血中のエクソソーム濃度:正常妊婦の週数別推移と妊娠高血圧腎症妊婦との比較2023

    • Author(s)
      成見莉紗、鈴木寛正、高橋宏典、他
    • Organizer
      日本胎盤学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The regulatory mechanism of extravillous trophoblast invasion through microRNAs2023

    • Author(s)
      Hironori Takahashi
    • Organizer
      アジア生殖免疫学会(Asian congress for reproductive immunology)
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] miR-675-5pは複数のmatrix metalloproteinaseの発現を上昇させ絨毛外栄養膜細胞の浸潤を促進する2020

    • Author(s)
      小古山学、大口昭英、高橋宏典、松原茂樹、瀧澤俊広
    • Organizer
      第35回日本生殖免疫学会学術集会
    • Related Report
      2020 Research-status Report
  • [Funded Workshop] アジア生殖免疫学会(Asian congress for reproductive immunology)2023

    • Related Report
      2022 Research-status Report
  • [Funded Workshop] 14th Philadelphia Prenatal Diagnosis Conference (online)2022

    • Related Report
      2022 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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